Full metadata record
DC Field | Value | Language |
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dc.contributor.author | Park, Bi-Oh | - |
dc.contributor.author | Kim, Seong Heon | - |
dc.contributor.author | Kong, Gye Yeong | - |
dc.contributor.author | Kim, Da Hui | - |
dc.contributor.author | Kwon, Mi So | - |
dc.contributor.author | Lee, Su Ui | - |
dc.contributor.author | Kim, Mun-Ock | - |
dc.contributor.author | Cho, Sungchan | - |
dc.contributor.author | Lee, Sangku | - |
dc.contributor.author | Lee, Hyun-Jun | - |
dc.contributor.author | Han, Sang-Bae | - |
dc.contributor.author | Kwak, Young Shin | - |
dc.contributor.author | Lee, Sung Bae | - |
dc.contributor.author | Kim, Sunhong | - |
dc.date.available | 2017-07-11T05:36:46Z | - |
dc.date.created | 2017-04-10 | - |
dc.date.issued | 2016-01 | - |
dc.identifier.issn | 0014-2999 | - |
dc.identifier.uri | http://hdl.handle.net/20.500.11750/2735 | - |
dc.description.abstract | GPR43/Free Fatty Acid Receptor 2 (FFAR2) is known to be activated by short-chain fatty acids and be coupled to Gi and Gq family of heterotrimeric G proteins. GPR43 is mainly expressed in neutrophils, adipocytes and enteroendocrine cells, implicated to be involved in inflammation, obesity and type 2 diabetes. However, several groups have reported the contradictory data about the physiological functions of GPR43, so that its roles in vivo remain unclear. Here, we demonstrate that a novel compound of pyrimidinecarboxamide class named as BTI-A-404 is a selective and potent competitive inverse agonist of human GPR43, but not the murine ortholog. Through structure-activity relationship (SAR), we also found active compound named as BTI-A-292. These regulators increased the cyclic AMP level and reduced acetate-induced cytoplasmic Ca2+ level. Furthermore, we show that they modulated the downstream signaling pathways of GPR43, such as ERK, p38 MAPK, and NF-κB. It was surprising that two compounds augmented the secretion of glucagon-like peptide 1 (GLP-1) in NCI-H716 cell line. Collectively, these novel and specific competitive inhibitors regulate all aspects of GPR43 signaling and the results underscore the therapeutic potential of them. © 2015 Elsevier B.V. All rights reserved. | - |
dc.language | English | - |
dc.publisher | Elsevier B.V. | - |
dc.title | Selective novel inverse agonists for human GPR43 augment GLP-1 secretion | - |
dc.type | Article | - |
dc.identifier.doi | 10.1016/j.ejphar.2015.12.010 | - |
dc.identifier.scopusid | 2-s2.0-84949758588 | - |
dc.identifier.bibliographicCitation | European Journal of Pharmacology, v.771, pp.1 - 9 | - |
dc.subject.keywordAuthor | GPR43 | - |
dc.subject.keywordAuthor | SCFA | - |
dc.subject.keywordAuthor | Inverse agonist | - |
dc.subject.keywordAuthor | BTI-A-404 | - |
dc.subject.keywordAuthor | BTI-A-202 | - |
dc.subject.keywordAuthor | GLP-1 | - |
dc.subject.keywordPlus | ACTIVATION | - |
dc.subject.keywordPlus | Agents Interacting With Transmitter, Hormone or Drug Receptors | - |
dc.subject.keywordPlus | Article | - |
dc.subject.keywordPlus | BETA-ARRESTINS | - |
dc.subject.keywordPlus | BTI-A-202 | - |
dc.subject.keywordPlus | BTI-A-404 | - |
dc.subject.keywordPlus | Bti A 292 | - |
dc.subject.keywordPlus | Bti A 404 | - |
dc.subject.keywordPlus | Calcium Ion | - |
dc.subject.keywordPlus | CHAIN FATTY-ACIDS | - |
dc.subject.keywordPlus | Competitive Inhibition | - |
dc.subject.keywordPlus | Controlled Study | - |
dc.subject.keywordPlus | Cyclic Amp | - |
dc.subject.keywordPlus | Cytoplasm | - |
dc.subject.keywordPlus | Drug Identification | - |
dc.subject.keywordPlus | Drug Potency | - |
dc.subject.keywordPlus | Drug Screening | - |
dc.subject.keywordPlus | Drug Selectivity | - |
dc.subject.keywordPlus | Drug Structure | - |
dc.subject.keywordPlus | ENTEROENDOCRINE CELLS | - |
dc.subject.keywordPlus | G Protein Coupled Receptor | - |
dc.subject.keywordPlus | GLP-1 | - |
dc.subject.keywordPlus | Glucagon Like Peptide 1 | - |
dc.subject.keywordPlus | GPR43 | - |
dc.subject.keywordPlus | GUT MICROBIOTA | - |
dc.subject.keywordPlus | High Throughput Screening | - |
dc.subject.keywordPlus | Immunoglobulin Enhancer Binding Protein | - |
dc.subject.keywordPlus | INFLAMMATORY RESPONSES | - |
dc.subject.keywordPlus | Inverse Agonist | - |
dc.subject.keywordPlus | KAPPA-B | - |
dc.subject.keywordPlus | Mitogen Activated Protein Kinase | - |
dc.subject.keywordPlus | Mitogen Activated Protein Kinase P38 | - |
dc.subject.keywordPlus | PEPTIDE-1 SECRETION | - |
dc.subject.keywordPlus | Priority Journal | - |
dc.subject.keywordPlus | PROTEIN-COUPLED RECEPTORS | - |
dc.subject.keywordPlus | Protein GPR43 | - |
dc.subject.keywordPlus | Protein Secretion | - |
dc.subject.keywordPlus | SCFA | - |
dc.subject.keywordPlus | Signal Transduction | - |
dc.subject.keywordPlus | SPECIES ORTHOLOGS | - |
dc.subject.keywordPlus | Structure Activity Relation | - |
dc.subject.keywordPlus | Unclassified Drug | - |
dc.citation.endPage | 9 | - |
dc.citation.startPage | 1 | - |
dc.citation.title | European Journal of Pharmacology | - |
dc.citation.volume | 771 | - |
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